Azides

ABSTRACT

Aliphatic substituted diolefinic acids and esters, and derivatives thereof, intermediates therefor, synthesis thereof and the control of insects.

United States Patent Henrick et al.

Feb. 4, 1975 AZIDES Inventors: Clive A. Henrick, Palo Alto, Calif;

Zoecon Corporation, Palo Alto, Calif.

Filed: Mar. 25, 1974 Appl. No.: 454,193

Related U.S. Application Data Division of Ser. No. 310,749, Nov. 30, 1972.

U.S. Cl 260/349, 424/226, 260/534 R,

260/487, 260/534 M, 260/484 R Int. Cl. C07c 117/00 Field of Search 260/349 [56] References Cited UNITED STATES PATENTS 3,719,666 3/l973 Anderson et al. 260/349 X Primary Examiner-John M. Ford Attorney, Agent, or Firm-Donald W. Erickson; Lee-Louis H. Priest [57] ABSTRACT Aliphatic substituted diolefinic acids and esters, and derivatives thereof, intermediates therefor, synthesis thereof and the control of insects.

4 Claims, N0 Drawings AZIDES This is a division of application Ser. No. 310,749, filed Nov. 30, l972.

This invention relates to novel aliphatic diolefinic compounds, intermediates therefor. synthesis thereof and the control of insects. Most particularly, the novel olefinic compounds of the present invention are represented by the following formula A:

m is zero or the positive integer one;

11 is the positive integer one or two;

each of R and R' is hydrogen or lower alkyl;

each of R, R R and R is lower alkyl;

R is hydrogen or methyl; and

R" is hydrogen, lower alkyl, cycloalkyl, lower alkenyl or lower alkynyl.

The compounds of formula A are useful for the control of insects. The utility of these compounds as insect control agents is believed to be attributable to their juvenile hormone activity. They are preferably applied to the immature insect, namely, during the embryo, larvae or pupae stages in view of their effect on metamorphosis and otherwise causing abnormal development leading to death or to inability to reproduce. These compounds are effective control agents for Heteropterans, such as Lygaeidae, Miridae and Pyrrhocoridae; Homopterans, such as Aphididae, Coccidae and Jassidae; Lepidopterans, such as Pyralidae, Noctuidae and Gelechiidae; Coleopterans, such as Tenebrionidae, Crysomelidae and Dermestidae; Dipterans, such as Culicidae, Muscidae and Sarcophagidae; and other insects. The compounds can be applied at low dosage levels of the order of 0.0] ,ug. to pg. per insect. Suitable carrier substances include liquid or solid inert carriers, such as water, acetone, xylene, mineral or vegetable oils, talc, vermiculite, natural and synthetic resins and silica. Treatment of insects in accordance with the present invention can be accomplished by spraying, dusting or otherwise contacting the insect, directly or indirectly, with one or more compounds of formula A. Generally, a concentration of less than of the active compound is employed. The formulations can include insect attractants, emulsifying agents or wetting agents to assist in the application and effectiveness of the active ingredient.

In the application of the compounds, there is generally employed a mixture of the C-2,3-trans and cis isomers, the C-2,3 and C-2,4 trans, trans isomer being the preferred embodiment for the control of insects.

In the description hereinafter each of RR R, and m is as defined above.

The compounds of the present invention can be prepared as outlined below:

I 5 (II In the above formulas, R is lower alkyl.

In the practice of the above outlined synthesis, an azide of formula lll is prepared from the corresponding chloride l by treatment with sodium azide, lithium azide, and the like, in an organic solvent'inert to the reaction such dimethylformamide, hexamethylphosphoric triamide or similar solvents.

Alternatively, the azide of formula Ill can be prepared from the corresponding hydroxy compound I by nitration as described by A. Michael et al., J. Amer. Chem. Soc, 57, 1268 (1935), and treatment of the nitrate with lithium azide, sodium azide, and the like in an organic solvent inert to the reaction such as dimethylformamide or similar solvents, Angew Chem. Int. Edr., l0. (l 97l p. 412.

The azide of formula lll is reduced to the amine of formula A (R and R is hydrogen) using hydrazine hydrate and Raney nickel in ethanol following the procedure described by R. D. Guthrie et al., J. Chem. Soc. 5288 (1963) and K. Ponsold, Chem. B012, 97, 3524 The secondary and tertiary amines of formula A are prepared from the primary amines of formula A described hereinabove with alkyl halides, such as methyl iodide, ethyl bromide, i-butyl iodide, and the like, in an organic solvent inert to the reaction such as benzene. methanol, ether or similar solvents, in the presence of a base such as sodium bicarbonate, potassium carbonate, or the like.

The esters of formula A are converted into the corresponding acids by hydrolysis with base, such as potassium carbonate or sodium carbonate in organic solvent, such as methanol or ethanol. Other esters of the present invention can be prepared by transesterification or conversion ofthe acid into the acid halide by treatment with thionyl chloride, oxalyl chloride, or the like, and then reacting the acid halide with the alcohol corresponding to the ester moiety desired.

The precursors of formula land I can be prepared as described in application Ser. No. l96,80(), filed Nov. 8, 1971, now US. Pat. No. 3,732,282, the disclosure of which is incorporated by reference.

The term lower alkyl," as used herein, refers to a straight or branched chain saturated aliphatic hydrocarbon group having a chain length of one to six carbon atoms, e.g., methyl, ethyl, propyl, i-propyl, n-butyl, sbutyl, t-butyl, pentyl and hexyl.

The term cycloalkyl, as used herein, refers to a cyclic alkyl group containing three to eight carbon atoms, e.g. cyclopropyl, cyclopentyl and cyclohexyl.

The term lower alkenyl, as used herein, refers to an ethylenically unsaturated hydrocarbon group, branched or straight chain, having a chain length oftwo to six carbon atoms, e.g., allyl, vinyl, 3-butenyl, 2- hexenyl and i-propenyl.

The term lower alky nyl," as used herein, refers to an acetylenically unsaturated hydrocarbon group, branched or straight chain, having a chain length of three to six carbon atoms, e.g. 2-propynyl, 3-pentynyl,

etc.

The following examples are provided to illustrate the practice of the present invention. Temperatures are given in degrees Centigrade.

EXAMPLE I To g. methyl ll-chloro-3,7,ll-trimethyldodeca- 2,4-dienoate in l ml. of dimethylformamide under argon is added 3 g..of sodium azide and the mixture is heated at l00 for 24 hr. Let cool. After pouring the mixture into water and extracting with pentane-ether (9:1), the organic fractions are washed with brine, dried over magnesium sulfate and evaporated to yield methyl l l-azido-3,7,l l-trimethyldodeca-2,4-dienoate.

EXAMPLE 2 Following the procedure of Example l each of the chloro compounds under Column l is treated with so dium azide to produce the corresponding azido compounds under Column ll.

methyl 1 l-chloro-3,7,l l-trimethyltridecu-2,4-

dienoate; ethyl l l-chloro-3,7-dimethyl-l l-ethyltrideca-2.4-

dienoate; ethyl l l-chloro-3,l l-dimethyl-7-ethyltrideca-2,4-

dienoate; methyl ll-chloro-3.7,l(),l ltetramethyldodeca-2,4-

dienoate; ethyl l l-chloro-3,7,l0,l l-tetramethyltrideca-2.4-

dienoate; ethyl l l-chloro-3,l(),l l-trimethyl-7-ethyltrideca- 2,4-dienoate; ethyl l l-chloro-3,l0-dimethyl-7,l l-diethyltrideca- 2,4-dienoate;

methyl l 0-chloro-3 .7 l O-trimethylundeca-Z ,4-

dienoate;

ethyl l0-chloro-3 l (l-dimethyl-7-ethyldodeca-2,4-

dienoate;

ethyl l0-chloro-3,6, l 0-trimethyldodeca-2,4-

dienoate;

methyl l0-chloro-3 ,7 ,9, l O-tetram ethyldodeca-2 ,4-

dienoate;

methyl l0-chloro-3 ,6,9, l O-tetramethyldodeca-Z ,4-

dienoate; ethyl 9-chloro-3,6,9-trimethylundeca-2,4-dienoate.

dienoate; ethyl lO-azido-3,6, l O-trimethyldodeca-2,4-dienoate; methyl l0-azido-3 ,7,9, l O-tetramethyldodeca-2,4-

dienoate; methyl dienoate; ethyl 9-azido-3,6,9-trimethylundeca-2,4-dienoate.

EXAMPLE 3 A cooled solution of 3.2 g. of nitric acid in 5 ml. of chloroform is slowly added to a solution of 7.5 g. methyl l l-hydroxy-3,l l-dimethyl-7-ethyltrideca-2,4-

lO-azido-3 ,6,9, l 0-tetramethyldodeca-2 ,4-

dienoate in 25 ml. of chloroform, cooled to 3(). The

mixture is stirred for 30 minutes keeping the temperature below 20, poured into ice-cold sodium bicarbonate solution, extracted with methylene chloride, washed with brine, dried and evaporated to yield methyl 1 l-nitrato-3,l l-dimethyl-7-ethyltrideca-2,4- dienoate (ll'; each of R, R" and R" is methyl, each of R and R is ethyl, R is hydrogen, m is one, n is two).

trideca-2,4-dienoate and 1.5 equivalent lithium azide are stirred in 50 ml. dimethylformamide for 24 hour at room temperature. After dilution with water and ex traction with ether, the ethereal extracts are washed with brine. dried over magnesium sulfate and evaporated toyield methyl ll-azide-3,ll-dimethyl-7-ethyltrideca-2.4-dienoate.

Using the foregoing procedure, the nitrates of Example 3 are treated with lithium azide to give the corresponding azidoesters.

EXAMPLE To 6.4 g. methyl 1 l-azido-3,l l-dimethyl-7-ethyltrideca-2,4-dien0ate in 300 ml. of ethanol under argon is added ml. of 85% hydrizine hydrate and 2 g. of Raney nickel. After stirring for 3 hour at room temperature, the catalyst is filtered off, and ether and saturated sodium chloride are added to the filtrate. The organic phase is washed with brine, dried and evaporated to yield methyl l l-amino-3.l l-dimethyl-7-ethyltrideca-Z,4-dienoate.

Similarly the azido compounds of Example 2 are reduced to the corresponding amines under Column III:

III

methyl l l-amino-3,7,l l-trimethyld0deca-2,4-

dienoate methyl ll-amino-3,7,l l-trimethyltrideca-2.4-

dienoate ethyl l l-amino-3,l l-dimethyl-7-ethyltrideca-2.4

dienoate methyl 1 1-amino-3,7,l 0,] l-tetramethyldodeca-2,4-

dienoate ethyl l Lamina-3.7.10.1 l-tetramethyltrideca-2,4-

dienoate ethyl l l-amino-3 ,l0,l l-trimethyl-7'ethyltridecadienoate ethyl l l-amino-3,l0-dimethyl-7 .l l-diethyltrideca- 2,4-dienoate methyl l0-amino-3 .7, l ()-trimethylundeca-2,4-

dienoate ethyl l0-amino-3, l 0-dimethyl-7-ethyldodeca-2.4-

dienoate ethyl l(l-amino-3.6.l(l-trimethyldodeca-2,4-dienoate methyl l (l-amino-3 .79. l (l-tetramethyldodeca-Z,4-

dienoate methyl l0-amino-3.6.9. l O-tetramethyldodeca-Z,4-

dienoate ethyl 9-aminc-3,6,9-trimethylundeca-Z.4-dien0ate EXAMPLE 6 3 g. ofmethyl l l-amino-3,7,l l-trimethyldodeca-ZA- dienoate in 20 ml. of benzene is added to a suspension of l equivalent sodium bicarbonate and l equivalent ethyliodide in 10 ml. of benzene. After stirring the mixture at room temperature for about 3 hours, methylene chloride is added and the mixture washed with brine. dried over sodium sulfate and evaporated to yield methyl l l-ethylamino-3,7.l l-trimethyldodeca-2.4- dienoate.

Other N-mono substituted amines of formula A (R is hydrogen, R is lower alkyl) are prepared by using an alkyl halide of the formula RX (R is lower alkyl. X is chloro, bromo or iodo) such as methyl iodide. butylbromide and the like in place of ethyl iodide.

The process of this example is repeated using the amines of Example 5 with an alkyl halide such as ethyl iodide, methyl iodide, butylbromide or the like to prepare the corresponding amines such as methyl l lethylamino-3,l l-dimethyl-7-ethyltrideca-2.4 dienoate; methyl 1 l methylamino-3,l l-dimethyl-7-ethyltrideca- 2,4-dienoate, ethyl l l-ethylamino-3,7,l l-trimethyltrideca-2,4-dienoate, isopropyl l lmethylamino-3,7.l ltrimethyldodeca-2.4-dienoate.

EXAMPLE 7 By use of the process of Example 6 with 2 equivalents each of sodium bicarbonate and alkylhalide, N- disubstituted amines of formula A (R R' lower alkyl) are prepared such as methyl ll-diethylamino- 3.7.1 l-trimethyldodeca-Z.4-dienoate, methyl 1 I- diethylamino-3,l l-dimethyl-7-ethyltrideca-2,4- dienoate, ethyl l l-dimethylamino-3,7.l l-trimethyltrideca-2,4-dienoate, isopropyl l l-dimethylamino- 3.7.l l-trimethyldodeca-Z.4-dienoate. etc.

EXAMPLE 8 By use of the process of Example 6 with a N-monosubstituted amine and l equivalent each of sodium bicarbonate and alkyl halide. N-disubstituted amines of formula A (R R is each lower alkyl) are prepared, e.g. methyl 1 l-methylethylamino-3,7,l l-trimethyldodeca-2.4-dienoate, methyl ll-methylbutylamino- 3,1 l-dimethyl-7-ethyltrideca-2,4-dienoate, etc.

EXAMPLE 9 l g. of methyl ll-diethylamino-3,7,l l-trimethyldodecaQA-dienoate, 60 ml. of methanol, 0.5 g. of sodium hydroxide and 6 ml. of water is stirred at about 30 for 3 days. The mixture is then diluted with water, neutralized and extracted with ether. The organic phase is washed, dried over sodium sulfate and evaporated to yield methyl 1 l-diethylamino-3,7,l l-trimethyldodeca-2,4-dienoic acid.

Similarly other aminoesters of formula A prepared in the Examples 5, 6, 7 and 8 give the corresponding acids.

EXAMPLE l0 l g. of thionyl chloride is added with stirring at room temperature to 0.5 g. of methyl 1 l-diethylamino- 3.7.l l-trimethyldodeca-2,4-dienoic acid in ether and stirred for about I hour. Excess thionyl chloride and ether is removed by evaporation. Then fresh ether and 2 equivalents isopropyl alcohol are added and the mixture is heated at about 50 for about 5 minutes. Excess alcohol is removed by evaporation to yield isopropyl l l-diethylamino-3,7,l l-trimethyldodeca-2,4-dienoate which is purified by chromotography.

Similarly by using other alcohols such as cyclopropyl alcohol, n-pentanol, t-butanol, 3-butenyl alcohol, 2- propynyl alcohol or i-propenyl alcohol, the corresponding esters are prepared. that is, cyclopropyl l l-diethylamino-3,7,l l-trimethyldodeca- 2,4-dienoate,

n-pentyl ll-diethylamino-3.7.l l-trimethyldodeca-2.4--

dienoate.

t-butyl l l-diethylamino-SJJ l-trimethyldodcca-ZA- dienoate,

3-butenyl ll-diethylamino-3.7.l l-trimethyldodeca- 2,4-dienoate,

prop-2'-yn-l -yl ll-diethylamino-3.7,l'l-trimethyldodeca-2,4-dienoate,

i-propenyl ll-diethylamino-3,7,l l-trimethyldodeca- 2,4-dienoate.

EXAMPLE ll Following the procedure of Example 10, each of the acids of formula A (prepared by the process of Example 9) is converted into the acid halide and then reacted with isopropanol to prepare the respective isopropyl ester.

What is claimed is:

l. A compound selected from those of the following formula (II) m is zero or the positive integer one; and

n is the positive integer one or two,

2. A compound according to claim I wherein m is one; n is two; and each of R, R R" and R is methyl or ethyl.

3. A compound according to claim 2 wherein each of R, R R" and R is methyl.

4. A compound according to claim 3 and R is hydrogen and R is methyl, ethyl or isopropyl. 

1. A COMPOUND SELECTED FROM THOSE OF THE FOLLOWING FORMULA (II)
 2. A compound according to claim 1 wherein m is one; n is two; and each of R1, R2, R3 and R4 is methyl or ethyl.
 3. A compound according to claim 2 wherein each of R1, R2, R3 and R4 is methyl.
 4. A compound according to claim 3 and R14 is hydrogen and R5 is methyl, ethyl or isopropyl. 